Method of using certain benzoylphenylureas to control fleas

ABSTRACT

Compounds of the formula (I) wherein R1 and R2 are H, methyl, or ethyl, have unexpected activity against fleas. Compounds wherein at least one of R1 and R2 is methyl or ethyl are novel.

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application Ser.No. 60/069,881, filed Nov. 8, 1996, and Divisional application of Ser.No. 08/963,506, filed Nov. 3, 1997, U.S. Pat. No. 5,886,221.

BACKGROUND OF THE INVENTION

This invention provides novel benzoylphenylurea insecticides and novelmethods of inhibiting cockroaches, ants, fleas, and termites.

A broad class of benzoylphenylurea insecticides is disclosed in U.S.Pat. No. 3,748,356. European Patent Application 263438 discloses thatcertain N-substituted phenyl-N'-substituted benzoyl-N-methylureas arehighly safe to beneficial aquatic Crustacea while exhibiting equal orsuperior insecticidal activities to non-alkylated analogs. Hexaflumuron,a commercially significant benzoylphenylurea, is disclosed in U.S. Pat.No. 4,468,405. Use of hexaflumuron in methods of controlling termites isdisclosed in WO 93/24011. Use of hexaflumuron to control cockroaches isdisclosed in WO 94/03066. The compoundN-[3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N'-(2,6-difluorobenzoyl)ureais disclosed in DE 3827133 and European Patent Application A 243,790,but there was no disclosure of the unexpected activity of the compoundagainst cockroaches, ants, fleas, and termites.

We have discovered that certain benzoylphenylurea compounds, some ofwhich are novel, have substantially greater activity againstcockroaches, ants, fleas, and termites than would have been expectedbased on comparison with the closest prior art, i.e., hexaflumuron.Another significant property of the novel compounds of the invention istheir surprisingly low toxicity to Daphnia.

SUMMARY OF THE INVENTION

The invention provides a method of controlling cockroaches, ants, fleas,or termites which comprises delivering a effective amount of a compoundof the formula (I): ##STR2## wherein R¹ and R² are H, methyl, or ethyl,to a location where control of cockroaches, ants, fleas, or termites isdesired.

More specifically, the invention provides:

A method of controlling cockroaches which comprises a compound of theformula (I), in an amount effective to control cockroaches, to alocation where control of cockroaches is desired;

A method of controlling ants which comprises delivering a compound ofthe formula (I), in an amount effective to control ants, to a locationwhere control of ants is desired.

A method of controlling fleas which comprises delivering a compound ofthe formula (I), in an amount effective to control fleas, to a locationwhere control of fleas is desired; and

A method of controlling termites which comprises delivering a compoundof the formula (I), in an amount effective to control termites, to alocation where control of termites is desired.

The invention also provides novel compounds of the formula (II) ##STR3##wherein R¹ ' and R² ' are H, methyl, or ethyl, provided that at leastone of R¹ ' and R² ' is methyl or ethyl.

DETAILED DESCRIPTION OF THE INVENTION

Intermediate 1: 2,6-difluorobenzoyl isocyanate ##STR4##

A mixture of 0.52 g of 2,6-difluorobenzamide and 0.33 ml of oxalylchloride was stirred under reflux in 15 ml 1,2-dichloroethane overnight.Solvent was removed under vacuum and 10 ml 1,2-dichloroethane was added.Solvent was removed under vacuum to leave the title intermediate, whichcould be used directly or dissolved in 1,2-dichloroethane and stored forfuture use.

Intermediate 2: 3,5-Dichloro-4-(1,1,2,3,3,3-hexafluoropropoxy)aniline##STR5##

To a solution of 2.0 g of 4-amino-2,6-dichlorophenol in 40 mLtetrahydrofuran at room temperature was added 0.7 g of 87% potassiumhydroxide. The mixture was warmed to 40° C. and stirred for 10 minutes,then chilled to 0° C. Hexafluoropropene was bubbled in for 5 minutes,and the mixture stirred at room temperature over night. It was thenconcentrated under vacuum to dryness. The residue was dissolved in 50 mLdichloromethane and washed with 20 mL brine solution. The organic layerwas separated and filtered through phase separation filter paper andthen concentrated under vacuum to an oil. This was diluted with 50 mLdichloromethane and 50 mL heptane and re concentrated to give 3.05 g of3,5-dichloro-4-(1,1,2,3,3,3-hexafluoropropoxy)aniline as a brown oil.Proton and ¹⁹ F nmr spectra were consistent with the proposed structure.

Intermediate 3:3,5-Dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)aniline ##STR6##

To a solution of 2.50 g 3,5-dichloro4-(1,1,2,3,3,3-hexafluoropropoxy)aniline in 60 mL acetonitrile under anatmosphere of nitrogen at room temperature there was added 2.57 g1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2] octane bis(tetrafluoroborate) SELECTFLUOR™ (Air Products) portion wise over a 10minute period. The mixture was warmed to 70° C. over a one hour period,then cooled to room temperature and poured into 100 mL of saturatedsodium bicarbonate solution. The product was extracted with 150 mL ethylacetate. The organic layer was separated, washed with 50 mL of brinesolution, separated, and dried over magnesium sulfate. The magnesiumsulfate was removed by filtration, and the filtrate was concentratedunder vacuum to give a dark oil 2.52 g. The product was chromatographedusing a Michel-Miller low pressure silica gel column eluted with 6:1heptane/ethyl acetate. Like fractions were pooled and concentrated undervacuum to a brown oil 1.19 g. The proton and ¹⁹ F nmr spectra wereconsistent with the proposed structure. Anal. calcd C₉ H₄ Cl₂ F₇ N₁ O₁ :C, 31.24; H, 1.17; N, 4.05. Found: C, 31.52; H, 1.15; N, 4.02.

Intermediate 4:3,5-Dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)-N-ethyl aniline##STR7##

To a solution of 0.28 g3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy) aniline in 8 mLglacial acetic acid at room temperature under an atmosphere of nitrogenwas slowly added 0.31 g sodium borohydride. The addition was carried outover a 1.5 hour period through a solid addition funnel between 25-34° C.with ice water cooling. The mixture was stirred at room temperature overnight. Then the reaction mixture was added to 80 mL water and the pH wascarefully adjusted to 7 by adding solid sodium carbonate. The productwas extracted with 80 mL ethyl acetate. The organic layer was separated,washed with brine solution, separated, and dried over magnesium sulfate.The magnesium sulfate was removed by filtration, and the filtrate wasconcentrated under vacuum to give a brown oil 0.29 g. The product waschromatographed using a Michel-Miller low pressure silica gel columneluted with 9:1 heptane/ethyl acetate. Like fractions were pooled andconcentrated under vacuum to give 0.19 g of a tan oil. ¹ H-NMR d 1.28(t, 3H), 3.17 (q, 4H), 3.95 (bs, 1H), 4.94-5.21 (md, 1H), 6.59 (d, 1H).Anal. calcd C₁₁ H₈ Cl₂ F₇ N: C, 35.31; H, 2.16; N, 3.74. Found: C,35.32; H, 2.14; N, 3.74.

Preparation of Products

Compound 1:N-[3,5-Dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N'-(2,6-difluorobenzoyl)urea##STR8##

To a solution of 1.31 g3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy) aniline in 5 mL1,2-dichloroethane under an atmosphere of nitrogen at room temperaturewas added 0.87 g 2,6-difluorobenzoyl isocyanate dissolved in 10 mLdichloroethane dropwise over a 10 minute period. The mixture wasstirred, warmed to 40° C. for a one hour period, then concentrated undervacuum to a brown solid 2.0 g. The mixture was chromatographed using aMichel-Miller low pressure silica gel column eluted with 4:1dichloromethane/heptane. Like fractions were pooled and concentratedunder vacuum to give 1.67 g of a light tan solid, mp 156-7° C. Protonand ¹⁹ F nmr spectra were consistent with the proposed structure. Anal.calcd C₁₇ H₇ Cl₂ F₉ N₂ O₃ : C, 38.58; H, 1.33; N, 5.29. Found: C, 38.64;H, 1.40; N, 5.44.

Compound 2:N-[3,5-Dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N'-(2,6-difluorobenzoyl)-N-ethylurea##STR9##

To a solution of 1.00 g3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)-N-ethyl anilinein 2 mL 1,2-dichloroethane under an atmosphere of nitrogen at roomtemperature there was added 0.54 g 2,6-difluorobenzoyl isocyanatedissolved in 6 mL dichloroethane dropwise over a 10 minute period. Themixture was stirred and warmed to 40° C. for a 1.5 hour period. Analysisby thin layer chromatography silica gel 4:1 heptane/ethyl acetateindicated incomplete reaction. To the mixture was added 0.13 g2,6-difluorobenzoyl isocyanate in 1.5 mL 1,2-dichloroethane, and themixture was warmed at 40° C. for 2.5 hour. Analysis by TLC indicatedcomplete reaction. The reaction mixture was concentrated under vacuum togive an oil 1.64 g, which was chromatographed using a Michel-Miller lowpressure silica gel column eluted with 4:1 heptane/ethyl acetate. Likefractions were pooled and concentrated under vacuum to give a whitesolid 0.87 g, mp 106-14° C. Proton nmr and mass spectra were consistentwith the proposed structure. Anal. calcd C₁₉ H₁₁ Cl₂ F₉ N₂ O₃ : C,40.95; H, 1.99; N, 5.03. Found: C, 40.89; H, 1.92; N, 5.03.

Compound 3:N-[3,5-Dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N'-(2,6-difluorobenzoyl)-N'-ethylurea ##STR10##

Dissolve 1.65 gN-[3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N'-(2,6-difluorobenzoyl)urea in 10 mL N,N-dimethylformamide and add 0.22 g 87% potassiumhydroxide. Chill to 0° C. and add 0.97 g iodoethane. Stir at 0° C. for a7 hour period. Store in freezer at 0° C. over night. Analysis by thinlayer chromatography silica gel dichloromethane shows product formingwith starting urea remaining. The reaction was treated as above at 0° C.for the next two days. Additional amounts of iodoethane, 1.94 g, and0.10 g 87% potassium hydroxide were added. Pour reaction mixture into 50mL brine solution and extract with 80 mL ethyl acetate. Separate organiclayer and dry over magnesium sulfate. Filter drying agent andconcentrate the filtrate under vacuum to a red oil 2.63 g. Chromatographusing a Michel-Miller low pressure silica gel column and elute with 2:1heptane/dichloromethane. Pool like fractions and concentrate undervacuum to 0.18 g of a pink solid, mp 105-06° C. Proton nmr and massspectra were consistent with the proposed structure. Anal. calcd C₁₉ H₁₁Cl₂ F₉ N₂ O₃ : C, 40.95; H, 1.99; N, 5.03. Found: C, 40.99; H, 1.85; N,4.98.

Biological Activity

German cockroach 2nd instars (Blattella germanica)

Continuous, low-dose ingestion exposure (treated cornmeal)

Rates: 0.19, 0.78, 3.12, 12.5, 50, 200 ppm

    ______________________________________                                                         LC.sub.50 (ppm)                                              Compound         21 days 42 days                                              ______________________________________                                        Compound 1       <2.2    <0.78                                                Compound 2       0.35    0.26                                                 Compound 3       8.0     1.5                                                  hexaflumuron     >200    >200                                                 ______________________________________                                    

Under continuous exposure, Compounds 1, 2, and 3 were far more activethan hexaflumuron.

German cockroach 2nd instars (Blattella germanica)

Limited ingestion exposure (48 hr) to treated cornmeal

Rates: 1, 10, 100, 1000, 10000 ppm

    ______________________________________                                                        LC.sub.50 (ppm)                                               Compound        21 days  42 days                                              ______________________________________                                        Compound 1      <22.2    <9.1                                                 Compound 2      21.1     12.8                                                 hexaflumuron    >10,000  >10,000                                              ______________________________________                                    

Under limited exposure, Compounds 1 and 2 were more potent thanhexaflumuron at both 21 and 42 days after exposure.

Cat Flea (Ctenocephalides felis)

Continuous exposure of larvae to treated media, impact on subsequentadult emergence

Rates: 0.1, 1.0, 10, 100, 1000 ppm

    ______________________________________                                        Compound       LC.sub.50 (ppm)                                                                         LC.sub.90 (ppm)                                      ______________________________________                                        Compound 1     2.8       22                                                   Compound 2     12.7      18.6                                                 hexaflumuron   65.7      333.5                                                ______________________________________                                    

Compounds 1 and 2 were both far more efficacious than hexaflumuronagainst cat fleas.

Subterranean Termite (Reticulitermes flavipes)

Continuous exposure (56 days) to treated paper

Rates: 0.78, 3.12, 12.5, 50, 200 ppm

    ______________________________________                                                    LC.sub.50 (ppm)                                                                             LT.sub.50 (days) for                                Compound   35 days    56 days 200 ppm trt                                     ______________________________________                                        Compound 1 31.2       <0.78   27.6                                            Compound 2 <0.78      <0.78   not calc.                                       hexaflumuron                                                                             >200       1.3     33.8                                            ______________________________________                                    

Under continuous exposure, Compounds 1 and 2 were more potent andquicker acting than hexaflumuron.

Subterranean Termite (Reticulitermes flavipes)

Limited exposure (7 days) with mortality determined at 14, 28, 42, and56 days

    ______________________________________                                        Compound    LT.sub.50 (days) for 10000 ppm treatment                          ______________________________________                                        Compound 1  23.7                                                              hexaflumuron                                                                              32.9                                                              ______________________________________                                    

Under limited exposure, a high rate of Compound 1 induced more mortalityearlier than did hexaflumuron.

Ant Studies

Laboratory ant bait studies were carried out with Red Imported Fire Ant(RIFA) (Solenopsis invicta) and Pharaoh Ant (Monomorium pharaonis).Chitin synthesis inhibitors, such as the compounds of the invention,control ants by killing the molting larvae and/or pupae and potentiallypreventing the hatching of eggs. Because adult workers are not affected,control is measured by effects on the brood. The studies involved 3-4day exposure to bait. These limited exposure studies more accuratelyrepresent real world bait availability than continuous exposure.

    ______________________________________                                                                    Time to Time to                                                               Achieve Achieve 90%                                        Concentration      50% Brood                                                                             Brood                                     Compound tested     Species Reduction                                                                             Reduction*                                ______________________________________                                        Compound 1                                                                             0.1%*      RIFA    2 wks   3 wks                                              0.1%       Pharaoh 4 wks   NA                                                                            (70% @ 13                                                                     wks)                                      Hexaflumuron                                                                           0.1%       RIFA    NA      NA                                                 0.25%      RIFA    4 wks   10 wks                                             0.1%       Pharaoh NA      NA                                        ______________________________________                                         *Only concentration tested.                                                   NA = did not achieve specified percent brood reduction.                  

Percent brood reduction achieved at end of study listed in parenthesis.

Compound 1 is significantly more potent than hexaflumuron based on ashort exposure study with RIFA.

Activity against Daphnia

48 hr exposure to treated water

    ______________________________________                                        Compound      LC.sub.50 (ppb) in water                                        ______________________________________                                        Compound 1    5.0                                                             Compound 2    >100                                                            Compound 3    >100                                                            Hexaflumuron  68.1                                                            ______________________________________                                    

Compounds 2 and 3, the alkylated derivatives of Compound 1, were muchless active against Daphnia than were Compound 1 and hexaflumuron; thisis surprising since the activities of Compound 1, 2, and 3 incockroaches are quite similar.

Formulations

In order to facilitate the application of the compounds of formula (I)to the desired locus, or to facilitate storage, transport or handling,the compound is normally formulated with a carrier and/or asurface-active agent.

A carrier in the present context is any material with which the compoundof formula (1) (active ingredient) is formulated to facilitateapplication to the locus, or storage, transport or handling. A carriermay be a solid or a liquid, including a material which is normallygaseous but which has been compressed to form a liquid. Any of thecarriers normally used or known to be usable in formulating insecticidalcompositions may be used.

Compositions according to the invention contain 0.0001 to 99.9% byweight active ingredient. Preferably, compositions according to theinvention contain 0.001 to 10.0% by weight of active ingredient thoughproportions as low as 0.0001% may be useful in some circumstances.

Suitable solid carriers include natural and synthetic clays andsilicates, for example natural silicas such as diatomaceous earths;magnesium silicates, for example talcs; magnesium aluminium silicates,for example attapulgites and vermiculites; aluminium silicates, forexample kaolinites, montmorillonites and micas; calcium carbonate;calcium sulphate; ammonium sulphate; synthetic hydrated silicon oxidesand synthetic calcium or aluminium silicates; elements, for examplecarbon and sulfur; natural and synthetic resins, for example coumaronneresins, polyvinyl chloride, and styrene polymers and copolymers; solidpolychlorophenols; bitumen; waxes; agar; and solid fertilizers, forexample superphosphates. Cellulose based materials, for example wood,sawdust, agar, paper products, cotton linter, or Methocel®, as well asthe other solid carriers that are themselves attractive to or at leastnon-repellant to termites are particularly suitable and preferable.Mixtures of different solids are often suitable. For example, a mixtureof wood flour and agar formulated as a moisture containing solid wouldbe preferable.

Suitable liquid carriers include water; alcohols, for exampleisopropanol and glycols; ketones, for example acetone, methyl ethylketone, methyl isobutyl ketone, isophorone and cyclohexanone; ethers;aromatic or aliphatic hydrocarbons, for example benzene, toluene andxylene; petroleum fractions, for example kerosene and light mineraloils; chlorinated hydrocarbons, for example carbon tetrachloride,perchloroethylene and trichloroethane; polar organic liquids, such asdimethyl formamide, dimethyl acetamide, dimethyl sulfoxide andN-methylpyrrolidone; oils derived from plants, such as corn oil andpeanut oil. Mixtures of different liquids are often suitable, forexample a mixture of isophorone with a polar organic solvent such asN-methylpyrrolidone, as are mixtures of solid and liquid carriers.

Pesticidal compositions are often formulated and transported in aconcentrated form which is subsequently diluted by the user beforeapplication. The presence of small amounts of a carrier which is asurface-active agent facilitates this process of dilution. Thus it issuitable to use at least one carrier in such a composition which is asurfaceactive agent. For example, the composition may contain at leasttwo carriers, at least one of which is a surface-active agent.

A surface-active agent may be an emulsifying agent, a dispersing agentor a wetting agent; it may be nonionic or ionic. Examples of suitablesurface-active agents include the sodium or calcium salts of polyacrylicacids and lignin sufonic acids; the condensation of fatty acids oraliphatic amines or amides containing at least 12 carbon atoms in themolecule with ethylene oxide and/or propylene oxide; fatty acid estersof glycerol, sorbitol, sucrose or pentaerythritol; condensates of thesewith ethylene oxide and/or propylene oxide; condensates of these withethylene oxide and/or propylene oxide; condensation products of fattyalcohol or alkyl phenols, for example p-octylphenol or p-octylcresol,with ethylene oxide and/or propylene oxide; sulfates or sulfonates ofthese condensation products; alkali or alkaline earth metal salts,preferably sodium salts, or sulfuric or sulfonic acid esters containingat least 10 carbon atoms in the molecule, for example sodium laurylsulphate, sodium secondary alkyl sulfates, sodium salts of sulfinatedcastor oil, and sodium alkylaryl sulfonates such as dodecylbenzenesulfonate; and polymers of ethylene oxide and copolymers of ethyleneoxide and propylene oxide.

Pesticidal compositions may for example be formulated as wettablepowders, dusts, granules, baits, solutions, emulsifiable concentrates,emulsions, suspension concentrates and aerosols.

Wettable powders usually contain 25, 50 or 75% weight of activeingredient and usually contain in addition to solid inert carrier, 3-10%weight of a dispersing agent and, where necessary, 0-10% weight ofstabilizer(s) and/or other additives such as penetrants or stickers.

Dusts are usually formulated as a dust concentrate having a similarcomposition to that of a wettable powder but without a dispersant, andare diluted in the field with further solid carrier to give acomposition usually containing 0.5-10% weight of active ingredient.

Granules are usually prepared to have a size between 10 and 100 BS mesh(1.676-0.152 mm), and may be manufactured by, for example, agglomerationor impregnation techniques. Generally, granules will contain 0.01-75%weight active ingredient and 0-10% weight of additives such asstabilizers, surfactants, slow release modifiers and binding agents. Theso-called "dry flowable powders" consist of relatively small granuleshaving a relatively high concentration of active ingredient. Ofparticular interest in current practice are the water dispersiblegranular formulations. These are in the form of dry, hard granules thatare essentially dust-free, and are resistant to attrition on handling,thus minimizing the formation of dust. On contact with water, thegranules readily disintegrate to form stable suspensions of theparticles of active material. Such formulation contain 90% or more byweight of finely divided active material, 3-7% by weight of a blend ofsurfactants, which act as wetting dispersing, suspending and bindingagents, and 1-3% by weight of a finely divided carrier, which acts as aresuspending agent.

Baits are prepared by, for example, combining a mixture of a suitablefood source, such as sawdust for termites or grain or meal forcockroaches, with an amount of active ingredient sufficient to providethe desired result; for example, from about 0.001% to about 20% weightactive ingredient and forming the mixture into a paste by the additionof about 1% to 5% of a water based binder such as agar. The paste-likemixture may be applied as is or may be packed into a housing such as ahollowed out wooden dowel or a plastic tube or bait station. In otherembodiments, sheets of paper or cardboard can be sprayed with or dippedin a diluted formulation containing the active ingredient. Baits are apreferable embodiment of the present invention.

Emulsifiable concentrates usually contain, in addition to a solvent and,when necessary, co-solvent, 10-50% weight per volume active ingredient,2-20% weight per volume emulsifiers and 0-20% weight per volume of otheradditives such as stabilizers, penetrants and corrosion inhibitors.

Suspension concentrates are usually compounded so as to obtain a stable,non-sedimenting flowable product and usually contain 10-75% weightactive ingredient, 0.5-15% weight of dispersing agents, 0.1-10% weightof suspending agents such as protective colloids and thixotropic agents,0-10% weight of other additives such as defoamers, corrosion inhibitors,stabilizers, penetrants and stickers, and water or an organic liquid inwhich the active ingredient is substantially insoluble; certain organicsolids or inorganic salts may be present dissolved in the formulation toassist in preventing sedimentation or as anti-freeze agents for water.

Aqueous dispersions and emulsions are compositions which may be obtainedby diluting a wettable powder or a concentrate with water. The saidemulsions may be of the water-in-oil or of the oil-in-water type, andmay have a thick `mayonnaise`-like consistency.

The method of applying a compound of Formula (I) to combat termitescomprises applying the compound, conveniently in a compositioncomprising the compound of Formula (I) and a carrier as described above,to a locus or area to be treated for the termites, such as soil ortimber, already subject to infestation or attack by termites or intendedto be protected from infestation by termites. The active ingredient is,of course, applied in an amount sufficient to effect the desired actionof combatting termite infestation. This dosage is dependent upon manyfactors, including the carrier employed, the method and conditions ofthe application, whether the formulation is present at the locus in theform of a film, or as discrete particles or as a bait, the thickness offilm or size of particles, the degree of termite infestation, and thelike.

Proper consideration and resolution of these factors to provide thenecessary dosage of the active ingredient at the locus to be protectedare within the skill of those versed in the art. In general, however,the effective dosage of the compound of the invention at the locus to beprotected--i.e., the dosage to which the termite has access--is of theorder of 0.001 to 1.0% based on the total weight of the composition,though under some circumstances the effective concentration may be aslittle as 0.0001% or as much as 2%, on the same basis.

When used to control cockroaches, it is preferred to use the activeingredient in a treated bait or as a surface treatment.

When used to control ants, it is preferred to use the active ingredientin a liquid bait or granular bait.

When used to control termites, it is preferred to use the activeingredient in a cellulose based bait.

When used to control fleas, it is preferred to use the active ingredienton a treated substrate.

Suitable formulations include granular, paste, or dust cockroach bait,SP or WP cockroach and/or flea sprayables, cellulose-based termitebaits, liquid or granular ant baits, feed-through or topical animaltreatment for fleas.

We claim:
 1. A method of controlling fleas which comprises delivering acompound of the formula (I) ##STR11## wherein R¹ and R² are H, methyl,or ethyl, in an amount effective to control fleas,to a location wherecontrol of fleas is desired.
 2. A method according to claim 1 whereinsaid compound is on a treated substrate.
 3. A method according to claim1 wherein said delivering is accomplished by applying a topicaltreatment to an animal.
 4. A method according to claim 1 wherein saiddelivering is accomplished by feeding an animal a composition thatcomprises said compound.
 5. A method according to claim 4 wherein saidanimal is a cat.
 6. A treated substrate for controlling fleas where saidtreated substrate comprises the compound of claim
 1. 7. A topicaltreatment for controlling fleas where said topical treatment comprisesthe compound of claim
 1. 8. A feed composition for controlling fleaswhere said feed composition comprises said compound of claim 1.